Gengo Osawa

Acute Hydrothorax in Continuous Ambulatory Peritoneal Dialysis – A Collaborative Study of 161 Centers

Follow-up studies on 3,195 patients from 161 centers in Japan undergoing continuous ambulatory peritoneal dialysis (CAPD) were performed for 1-104 months to clarify the incidence as well as the clinical features of acute hydrothorax. In these studies, 50 patients (1.6%) developed this complication. Twenty-seven (54%) were men, and 23 (46%) were women, ranging in age from 6 to 79 (average 49) years. The interval between onset of CAPD and hydrothorax ranged from 1 day to 8 years. Four had left-sided, and 2 had bilateral hydrothorax, but the majority (88%) were right-sided. Dyspnea was experienced by 37 of these 50 patients, but the remaining 13 (26%) patients were asymptomatic. Hydrothorax was fully resolved in 27 of them following a brief interruption of CAPD or the combined use of small exchange volumes in a semi-sitting position and pleurodesis with tetracycline or other agents. The remaining 23 patients (46%) were switched to hemodialysis permanently. Despite recurrence, 1 patient continued successfully on CAPD. It was concluded that acute hydrothorax is one important possible complication, although the risk may be low. Constant surveillance is necessary to detect pleural effusions in patients during CAPD.

Population analysis of mesothelium in situ and in vivo exposed to bicarbonate-buffered peritoneal dialysis fluid.

Population analysis of mesothelium (PAM) done using the in vivo and almost in situ technique of mesothelial cell imprints revealed that lactate-buffered solutions had detrimental effects upon cell viability, that high glucose concentration affected cytokinesis, whereas the association of both components led to a decreased density population of cells showing a larger surface area. In the present study, PAM was done on mesothelium of mice exposed to bicarbonate-buffered peritoneal dialysis fluid (BBF) with glucose concentrations of 1.5 and 4.25%, for periods of time of 2 h, 15 and 30 days, as well as after recovery intervals of 7 and 30 days, BBF did not affect mesothelial cell viability. However, the increased incidence of multinucleated cells observed with both glucose concentrations, more marked with the 4.25% solution, suggests a detrimental effect upon the mechanism of cytokinesis. Furthermore, the higher the glucose concentration, the higher the mean-cell cytoplasmic surface area and the proportion of large cells, both resulting most probably from the regulatory volume increase developed by cells continuously exposed to hyperosmolar fluids. So far, evidence presented in this study suggests once more that BBF is remarkably more compatible with a higher quality of adaptation and survival of the exposed mesothelium than the lactated fluid. The question of whether the alterations induced by the high concentration of glucose result from a specific effect of glucose, by the coincidental hyperosmolarity, or by both still remains unanswered.

A randomized open-label comparative study of conventional therapy versus mizoribine onlay therapy in patients with steroid-resistant nephrotic syndrome (postmarketing survey)

BackgroundA previous double-blind 24-week clinical trial of mizoribine (MZ) vs placebo in steroid-resistant primary nephrotic syndrome (SRPNS) showed that MZ was more effective than placebo in reducing the rate of deterioration of renal function. The present study was conducted to evaluate the efficacy and safety of MZ in patients with SRPNS after 2 years’ treatment.MethodsA multicenter randomized open-label controlled trial in patients with SRPNS was conducted as a 2-year prospective postmarketing study.ResultsThere was a significant imbalance in the baseline serum albumin level (s-Alb) between the conventional therapy (CT) and MZ onlay therapy groups. Early dropouts were more frequent in the subset of patients in the CT group having a baseline s-Alb ≤3 g/dl. Therefore, the primary analysis (urinary protein level (UP)-improving effect) was performed using a mixed-effects model, with stratification according to the baseline s-Alb value. The analysis revealed that, in the subset of 34 patients with membranous nephropathy (MN) within the stratum of patients with baseline s-Alb ≤3 g/dl (n = 52), the rate of change (slope of change in the UP level/month), in terms of the log (UP+0.2), was −0.0577 in those allocated to the MZ group and −0.0227 in those allocated to the CT group (P = 0.058). In the stratum of patients with a baseline s-Alb >3 g/dl (n = 97), there were no significant differences in the UP between the two treatment groups. Hence, MZ onlay therapy was not considered to be efficacious in this group of patients. No serious adverse reactions to the drug were observed.ConclusionsThe present study yielded significant results, in that it suggested the possibility that long-term MZ therapy may afford further reduction of the UP, in addition to that obtained following CT, in particular, in MN patients in a severe nephrotic state.

Hypothesis : Is accumulation of a furan dicarboxylic acid (3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid) related to the neurological abnormalities in patients with renal failure ?

The plasma concentrations of a lipophilic furan dicarboxylic acid (3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid; 5-propyl FPA), which is highly bound to albumin and not removed by haemodialysis,

Myelofibrosis Secondary to Renal Osteodystrophy

A hemodialyzed women with secondary hyperparathyroidism who recovered well from myelofibrosis after a total parathyroidectomy with autotransplantation of parathyroid tissue to the forearm (PTx) is described. Before the operation, she had received regular transfusions to maintain an adequate hematocrit even under recombinant human erythropoietin (rhEpo) therapy. She showed splenomegaly and leukoerythroblastosis was present in her peripheral blood. A bone marrow biopsy and bone marrow scintigraphy confirmed the diagnosis of myelofibrosis. After PTx, her hematocrit gradually increased without any transfusion. It has been maintained around 35% now 16 months since the operation. Her spleen has also gradually decreased in size. In addition, no leukoerythroblastosis has been found in the peripheral blood. Serial follow-up scintigraphy of bone marrow revealed a decline in extramedullary hematopoiesis. These findings indicated that her myelofibrosis was the result of secondary hyperparathyroidism, and that this complication is potentially reversible if accurate treatment is given. Physicians dealing with the end-stage renal disease should be aware of this complication to avoid additional transfusions.

Relevance of resistive index ultrasonographic measurement in renal transplantation

The usefulness of the ultrasonographic measurement of resistive index (RI) is not yet fully understood. To obtain a better definition of its relevance in renal disease we studied this parameter in a group of 212 renal transplant patients, aged between 15 and 55 years: 81 first grafts with an excellent renal function, 44 hypertensive patients, 30 type II diabetics, 29 cases of chronic graft dysfunction, 28 cases during an episode of acute rejection. RI was measured in three different renal vascular areas: prerenal, interlobar and cortical. A two-way analysis of variance showed a statistical significance for the site of RI sampling and the type of pathology. There was no interaction between the two variables studied (p = 0.30). Plasma creatinine levels, analyzed as covariate, showed a high statistical correlation with RI values (p = 0.0001). The mean RI of the 80 transplanted patients with normal creatinine plasma levels showed a remarkable homogeneity and a statistically significant progressive reduction of the values from the main renal artery to the interlobar and cortical vessels (p = 0.00001). In the other groups a greater dispersion of data was present. RI values significantly increased in hypertensive and diabetic patients (p = 0.05) but more in acute rejection (p = 0.0001) or chronic graft dysfunction (p = 0.01). In acute rejection and in chronic graft dysfunction the curve of RI values tended to become flat, while in hypertensive and diabetic patients the aspect of the curve became steeper. In conclusion, RI is a hemodynamic index that reflects the vascular status of the explored area and is not only the simple expression of reduction of the kidney functional units. The differences observed in the various kidney areas stress the importance of measuring this parameter at more than one vascular site. The increase in RI values on the kidney cortex vessels is likely to be an index of glomerular hyperfiltration. If this hypothesis is true the measure of RI might be a reliable method for diagnosing in the kidney vascular damage, glomerular hypertension and hypertrophy.

Treatment of a Patient with End-Stage Renal Disease, Severe Iron Overload and Ascites by Weekly Phlebotomy Combined with Recombinant Human Erythropoietin

A 41-year-old hemodialyzed woman developed ascites and was found to have secondary iron overload. The dose of administered iron was approximately 11-12 g, and her serum ferritin level was 15,000 ng/ml (15,000 micrograms/l). There were no signs of congestive heart failure, fluid overload, or liver cirrhosis. A program of weekly phlebotomy combined with recombinant human erythropoietin (rhEPO) therapy was tried to eliminate the iron congestion. After 9 months of this therapy, about 5 g of iron had been removed. The ascites completely disappeared, and her serum ferritin level fell to 5,800 ng/ml (5,800 micrograms/l). This suggests that such combined therapy would be useful when iron overload must be corrected rapidly. Before therapy, the sterile ascitic fluid showed exudative characteristics with 3.7 g/dl (37 g/l) of total protein. The serum-ascites albumin difference was 0.6 g/dl (6 g/l), and the fluid contained 1,400 inflammatory cells/mm3 (1.4 X 10(9)/l). Notably, the serum-ascites albumin difference increased in parallel with iron elimination. These findings suggested that iron deposition may have played a role in changing the permeability of the peritoneum, or in impairing lymphatic drainage, both of which are presumed to be pathogenetic factors of nephrogenic ascites.

Human trehalase : Characterization, localization, and its increase in urine by renal proximal tubular damage

By using polymerase chain reaction, cDNA encoding human renal trehalase has been isolated. The partial amino acid sequence deduced by the cDNA showed homologies in rabbit, Tenebrio molitor and silkworm trehalase. Northern blots showed renal trehalase mRNA to be about 2.0 kb. To examine the properties of renal and urinary human trehalase, the trehalase cDNA was inserted in the pMAL-cRI vector downstream from the malE gene, which encodes maltose-binding protein. Transfection of the recombinant pMAL-cRI in Escherichia coli provided high levels of expression of the maltose binding protein-trehalase fusion protein. A rabbit was immunized with purified fusion protein, and antihuman trehalase antibodies were obtained. Immunoblot analysis disclosed that renal and urinary trehalase exhibited a molecular mass of about 75 kDa. Analysis by indirect fluorescent microscopy demonstrated that the enzyme located in only proximal tubular cells. Urinary trehalase activity was low in the healthy infants and elevated in patients with asphyxia. Markedly high activity was observed in a patient with Lowe syndrome. The immunoreactive urinary trehalase with 75 kDa was increased dependent on the elevation of the activity. On the basis of these findings, we conclude that the increase of urinary trehalase reflects the extent of renal tubular damage, and we propose that urinary trehalase can be a specific marker of renal tubular damage.

Antimouse Laminin Antibodies in IgA Nephropathy and Various Glomerular Diseases

IgG, IgA and IgM class antibodies to mouse laminin and human fibronectin in sera from patients with various glomerular diseases (50 cases of IgA nephropathy, 5 cases of minimal-change nephrotic syndrome; 6 cases of membranous nephropathy, 5 cases of systemic lupus erythematosus, 2 cases of Henoch-Schönlein purpura, 3 cases of poststreptococcal nephritis and 4 cases of preeclampsia) and from 30 normal controls were tested using a solid-phase enzyme-linked immunosorbent assay method. IgA antimouse laminin antibody titers in sera from IgA nephropathy patients were significantly higher (p less than 0.05) than in controls. There were no statistical differences in IgA antimouse laminin antibody titers between patients with other glomerular diseases and normal controls. IgM antimouse laminin antibody was significantly raised (p less than 0.01) in sera from patients with preeclampsia. The reaction of mouse laminin with the IgA nephropathy and preeclampsia sera on each of the IgA and IgM assay systems was inhibited by the antigen at up to 5 micrograms/ml. However, it was not inhibited by anti-C3d, anti-C1q, anti-J chain and antisecretory component sera or saccharides. The reaction of mouse laminin with an exceptionally high-titer IgA antimouse laminin antibody serum from a normal control on the IgA assay system was clearly inhibited by 1 mM of melibiose, which contains alpha-galactosyl residues. The same concentration of melibiose, however, did not inhibit the reaction of mouse laminin with IgA nephropathy sera on the same assay system. Treatment of mouse laminin with alpha-galactosidase did not alter any binding from IgA nephropathy sera but binding was lost from an exceptionally high-titer normal control serum. There were no correlations between serum IgA level and IgA antimouse laminin antibody titer in sera from IgA nephropathy patients. Immunoblot techniques revealed the presence of antibody in sera from IgA nephropathy patients reacting with both subunits A and B of laminin, somewhat stronger with laminin A. None of the sera tested contained antifibronectin antibodies. These results indicate that the IgA antimouse laminin antibody is a specific antibody in IgA nephropathy and might play a role in the pathogenesis of the nephritis since mouse laminin and human mesangial laminin present a common epitope.

Malignant Hypertension and Antiphospholipid Syndrome

Dr. A.E. Sirvent, Avda Orihuela 4, 6 D, E-03006 Alicante (Spain) Dear Sir, The kidney is now recognized as another target organ in the antiphospholipid syndrome (AS) [1]. Renal involvement is consistent with thrombosis of the major renal vessels and noninflammatory microvascular disease [2-4]. In the clinical findings renal failure has been emphasized over systemic hypertension. We report here on a patient with systemic malignant hypertension and throm-botic microangiopathy (TM) with no other occlusive complications. A 29-year-old man was hospitalized with acute renal failure during a malignant hypertensive episode, after developing hypertension in the 3 months prior to admission. Thrombocytopenia was also detected. Physical examination showed: blood pressure 230/ 130 mm Hg, grade IV retinal changes, no abdominal bruits were heard; the signs were compatible with congestive heart failure. The most significant laboratory findings were: hemoglobin lOg/dl, WBC 14,000/μl (normal differential count), platelets 47,000/μl, normal coagulation tests, fíbrinogen 490 mg/dl and schistocytes on a peripheral blood smear. Urea was 35 mmol/l, creatinine 884 μmol/l, LDH 971 U/l, haptoglobin 11 mg/dl, and urine contained proteinuria 2.1 g/day, 10-15 erythrocytes/hpf. Chest X-ray revealed pulmonary edema and cardiomegaly, and echo-cardiography indicated left ventricular hypertrophy, normal ejection fraction and mild mitral regurgitation. The abdominal ultrasound showed a right kidney of 11.9 cm and a left kidney of 8.7 cm. No evidence of kidney infarction was seen in the renal CT scan. The magnetic resonance angiogram disclosed normal aorta and renal arteries. The following laboratory data were negative or normal: urine cultures, urine catecholamines and VMA, HBsAg, serology for HCV, cryoglobulins, rheumatoid factor, ANCA, anti-GBM, ANA, anti-DNA, anti-SSA (Ro), anti-SSB (La), anti-Sm, anti-RNP antibodies, C3, C4, VDRL, brain CT, cystography, lupus anticoagulant; anticardiolipin antibodies (aCL) IgG 63.3 GPL/ml (n.v. < 23), IgM 3.1 MPL/ml (n.v. < 11), and repeated after 8 weeks, IgG 40 GPL/ml (ELISA). Antiplatelet antibodies were positive. The kidney biopsy showed TM; no deposits were noted in the immunofluores-cence study. Blood pressure was controlled. An increase in platelets and normalization of LDH was achieved following plasma exchange with FFP as the replacement fluid; upon withdrawal of the plasma exchange, thrombocytopenia recurred. After receiving the aCL determination